42 research outputs found

    Kaposi's sarcoma in an HIV-positive person successfully treated with paclitaxel

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    Epidemic Kaposi's sarcoma is one of the malignant neoplasms, which can develop in HIV-infected patients. Although the prevalence of HIV infection is reported to be high in Asian countries, Kaposi's sarcoma is rarely reported. We report a case of Kaposi's sarcoma involving the skin and oral mucosa along with extensive bilateral lymphedema of lower extremities, treated successfully with paclitaxel and antiretrovirals

    Effect of tyrosin kinase inhibitors on NK Cell and ILC3 development and function

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    Tyrosin kinase inhibitors (TKI) sharply improved the prognosis of Chronic Myeloid Leukemia (CML) and of Philadelphia+ Acute Lymphoblastic Leukemia (Ph+ALL) patients. However, TKI are not curative because of the development of resistance and lack of complete molecular remission in the majority of patients. Clinical evidences would support the notion that patient's immune system may play a key role in preventing relapses. In particular, increased proportions of terminally differentiated CD56+CD16+CD57+ NK cells have been reported to be associated with successful Imatinib therapy discontinuation or with a deep molecular response in Dasatinib-treated patients. In view of the potential role of NK cells in immune-response against CML, it is important to study whether any TKI have an effect on the NK cell development and identify possible molecular mechanism(s) by which continuous exposure to in vitro TKI may influence NK cell development and repertoire. To this end, CD34+ hematopoietic stem cells (HSC) were cultured in the absence or in the presence of Imatinib, Nilotinib, or Dasatinib. We show that all compounds exert an inhibitory effect on CD56+ cell recovery. In addition, Dasatinib sharply skewed the repertoire of CD56+ cell population, leading to an impaired recovery of CD56+CD117-CD16+CD94/NKG2A+EOMES+ mature cytotoxic NK cells, while the recovery of CD56+CD117+CD94/NKG2A ROR\u3b3t+ IL-22-producing ILC3 was not affected. This effect appears to involve the Dasatinib-mediated inhibition of Src kinases and, indirectly, of STAT5-signaling activation in CD34+ cells during first days of culture. Our studies, reveal a possible mechanism by which Dasatinib may interfere with the proliferation and maturation of fully competent NK cells, i.e., by targeting signaling pathways required for differentiation and survival of NK cells but not of ILC3

    Effect of Tyrosin Kinase Inhibitors on NK Cell and ILC3 Development and Function

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    Tyrosin kinase inhibitors (TKI) sharply improved the prognosis of Chronic Myeloid Leukemia (CML) and of Philadelphia+ Acute Lymphoblastic Leukemia (Ph+ALL) patients. However, TKI are not curative because of the development of resistance and lack of complete molecular remission in the majority of patients. Clinical evidences would support the notion that patient's immune system may play a key role in preventing relapses. In particular, increased proportions of terminally differentiated CD56+CD16+CD57+ NK cells have been reported to be associated with successful Imatinib therapy discontinuation or with a deep molecular response in Dasatinib-treated patients. In view of the potential role of NK cells in immune-response against CML, it is important to study whether any TKI have an effect on the NK cell development and identify possible molecular mechanism(s) by which continuous exposure to in vitro TKI may influence NK cell development and repertoire. To this end, CD34+ hematopoietic stem cells (HSC) were cultured in the absence or in the presence of Imatinib, Nilotinib, or Dasatinib. We show that all compounds exert an inhibitory effect on CD56+ cell recovery. In addition, Dasatinib sharply skewed the repertoire of CD56+ cell population, leading to an impaired recovery of CD56+CD117−CD16+CD94/NKG2A+EOMES+ mature cytotoxic NK cells, while the recovery of CD56+CD117+CD94/NKG2A−RORγt+ IL-22-producing ILC3 was not affected. This effect appears to involve the Dasatinib–mediated inhibition of Src kinases and, indirectly, of STAT5-signaling activation in CD34+ cells during first days of culture. Our studies, reveal a possible mechanism by which Dasatinib may interfere with the proliferation and maturation of fully competent NK cells, i.e., by targeting signaling pathways required for differentiation and survival of NK cells but not of ILC3

    Chikungunya Outbreak in the Republic of the Congo, 2019—Epidemiological, Virological and Entomological Findings of a South-North Multidisciplinary Taskforce Investigation

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    The Republic of Congo (RoC) declared a chikungunya (CHIK) outbreak on 9 February 2019. We conducted a ONE-Human-Animal HEALTH epidemiological, virological and entomological investigation. Methods: We collected national surveillance and epidemiological data. CHIK diagnosis was based on RT-PCR and CHIKV-specific antibodies. Full CHIKV genome sequences were obtained by Sanger and MinION approaches and Bayesian tree phylogenetic analysis was performed. Mosquito larvae and 215 adult mosquitoes were collected in different villages of Kouilou and Pointe-Noire districts and estimates of Aedes (Ae.) mosquitos’ CHIKV-infectious bites obtained. We found two new CHIKV sequences of the East/Central/South African (ECSA) lineage, clustering with the recent enzootic sub-clade 2, showing the A226V mutation. The RoC 2019 CHIKV strain has two novel mutations, E2-T126M and E2-H351N. Phylogenetic suggests a common origin from 2016 Angola strain, from which it diverged around 1989 (95% HPD 1985–1994). The infectious bite pattern was similar for 2017, 2018 and early 2019. One Ae. albopictus pool was RT-PCR positive. The 2019 RoC CHIKV strain seems to be recently introduced or be endemic in sylvatic cycle. Distinct from the contemporary Indian CHIKV isolates and in contrast to the original Central-African strains (transmitted by Ae. aegypti), it carries the A226V mutation, indicating an independent adaptive mutation in response to vector replacement (Ae. albopictus vs Ae. aegypti)

    Ambulatory Multi-Drug Resistant Tuberculosis Treatment Outcomes in a Cohort of HIV-Infected Patients in a Slum Setting in Mumbai, India

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    Background: India carries one quarter of the global burden of multi-drug resistant TB (MDR-TB) and has an estimated 2.5 million people living with HIV. Despite this reality, provision of treatment for MDR-TB is extremely limited, particularly for HIV-infected individuals. Médecins Sans Frontières (MSF) has been treating HIV-infected MDR-TB patients in Mumbai since May 2007. This is the first report of treatment outcomes among HIV-infected MDR-TB patients in India. Methods: HIV-infected patients with suspected MDR-TB were referred to the MSF-clinic by public Antiretroviral Therapy (ART) Centers or by a network of community non-governmental organizations. Patients were initiated on either empiric or individualized second-line TB-treatment as per WHO recommendations. MDR-TB treatment was given on an ambulatory basis and under directly observed therapy using a decentralized network of providers. Patients not already receiving ART were started on treatment within two months of initiating MDR-TB treatment. Results: Between May 2007 and May 2011, 71 HIV-infected patients were suspected to have MDR-TB, and 58 were initiated on treatment. MDR-TB was confirmed in 45 (78%), of which 18 (40%) were resistant to ofloxacin. Final treatment outcomes were available for 23 patients; 11 (48%) were successfully treated, 4 (17%) died, 6 (26%) defaulted, and 2 (9%) failed treatment. Overall, among 58 patients on treatment, 13 (22%) were successfully treated, 13 (22%) died, 7 (12%) defaulted, two (3%) failed treatment, and 23 (40%) were alive and still on treatment at the end of the observation period. Twenty-six patients (45%) experienced moderate to severe adverse events, requiring modification of the regimen in 12 (20%). Overall, 20 (28%) of the 71 patients with MDR-TB died, including 7 not initiated on treatment. Conclusions: Despite high fluoroquinolone resistance and extensive prior second-line treatment, encouraging results are being achieved in an ambulatory MDR-T- program in a slum setting in India. Rapid scale-up of both ART and second-line treatment for MDR-TB is needed to ensure survival of co-infected patients and mitigate this growing epidemic.</br

    Emergence of new SARS-CoV-2 Variant of Concern Omicron (B.1.1.529) - highlights Africa's research capabilities, but exposes major knowledge gaps, inequities of vaccine distribution, inadequacies in global COVID-19 response and control efforts

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    Nearly two years since the start of the SARS-CoV-2 pandemic, which has caused over 5 million deaths, the world continues to be on high COVID-19 alert. The World Health Organization (WHO), in collaboration with national authorities, public health institutions and scientists have been closely monitoring and assessing the evolution of SARS-CoV-2 since January 2020 (WHO 2021a; WHO 2021b). The emergence of specific SARS-CoV-2 variants were characterised as Variant of Interest (VOI) and Variant of Concern (VOC), to prioritise global monitoring and research, and to inform the ongoing global response to the COVID-19 pandemic. The WHO and its international sequencing networks continuously monitor SARS-CoV-2 mutations and inform countries about any changes that may be needed to respond to the variant, and prevent its spread where feasible. Multiple variants of the virus have emerged and become dominant in many countries since January 2021, with the Alpha, Beta, Gamma and Delta variants being the most prominent to date. (Table 1)

    Kaposi's sarcoma in an HIV-positive person successfully treated with paclitaxel

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    Epidemic Kaposi′s sarcoma is one of the malignant neoplasms, which can develop in HIV-infected patients. Although the prevalence of HIV infection is reported to be high in Asian countries, Kaposi′s sarcoma is rarely reported. We report a case of Kaposi′s sarcoma involving the skin and oral mucosa along with extensive bilateral lymphedema of lower extremities, treated successfully with paclitaxel and antiretrovirals

    Contributo di ricerca 286/2019. Sicurezza stradale. Elementi per la formulazione di nuove politiche

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    Sicurezza stradale. Elementi per la formulazione di nuove politiche- Indice #6- Capitolo 1. Premessa e obiettivi del lavoro #10- Capitolo 2. Il percorso analitico #12- Capitolo 3. La classificazione secondo categorie funzionali #26- Capitolo 4. Le tematiche innovative nella sicurezza stradale #4

    Network Screening for Smarter Road Sites: A Regional Case

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    Road safety has been a main societal and policy issue in many European countries since the early years of last decade. After the 2000-2010 Road Safety Programme launched by the European Commission, in 2011 the Commission adopted the new 2020 programme, even more demanding than the previous. As the societal consequences of road casualties are increasingly perceived as a core dimension of smart mobility, road safety system is now facing new challenges. Current mobility shifts to softer and greener transportation means raise new safety concerns for an increasingly larger share of vulnerable road users. The need to integrate road safety requirements with other residential, mobility, and environmental policies calls for a more detailed understanding of the phenomenon at different spatial levels and with different observation lenses. The pilot study described in this paper is a contribution to this end. It aims at identifying the accident prone sites of the regional road network to help prioritizing safety interventions, by the regional administration having road planning responsibilities. The study develops a screening approach to select hazardous road locations, outside urban premises, from the Piedmont provincial and state roads. The most recent data for the 2010-2012 years were considered, drawn from the ISTAT road accident database, managed by the CMRSS. The procedure consists of the following steps: identification of the elementary road sections to be screened, through a GIS analysis; definition of the screening groups (road sections have been subdivided in 4 length classes); definition of the selection criteria, with two severity thresholds based on the crash density; classification of the elementary road sections by severity thresholds
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